Multiple sclerosis (MS) is a chronic, unpredictable neurological disease with onset during the most productive years of one's life and an absence of convincing disease-modifying treatment. This combination creates an uncommonly stressful illness that exerts a powerful impact upon an individual's quality of life (QOL). Those with MS have lower QOL than non-diseased and diseased populations. Obviously, mitigating reductions in QOL of those with MS is an important research direction. This might be accomplished by understanding factors that influence QOL in those with MS. Participation in physical activity is a modifiable lifestyle factor that positively influences QOL among those with MS. Disability, mood, self-efficacy, social support, pain, and fatigue are additional influences on QOL among those with MS. Based on conceptual models and recent research, the positive effect of physical activity on QOL among those with MS might be accounted for by intermediate factors, namely disability, mood, self-efficacy, social support, pain, and fatigue. The proposed study involves (1) an examination of the physical activity and QOL relationship and (2) an evaluation of variables that account for the influence of physical activity on QOL in individuals with MS. This will be accomplished using a longitudinal research design with a convenience sample of 250 MS patients. We hypothesize that there will be a positive relationship between physical activity and QOL among those with MS, and this relationship will be accounted for by disability, mood, self-efficacy, social support, pain, and fatigue. That is, physical activity will be associated with improved QOL through reduced disability, depression, anxiety, pain, and fatigue and enhanced self-efficacy and social support. Our hypotheses will be addressed using advanced data analytic techniques, namely covariance structure analysis. The public health significance of this line of research is that physical activity is a modifiable lifestyle factor that has a potentially profound role in improving the QOL of those with MS. Encouraging participation in physical activity among those with MS, although challenging, is crucial for meaningful improvements in one's QOL. Before encouraging participation in physical activity, additional research is required that supports the link between physical activity and QOL and identifies factors that account for this relationship. [unreadable] [unreadable] [unreadable]